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Background: Clinical data are limited in patients with vitiligo with or without autoimmune thyroid disease. Objectives: The objective of the study was to investigate the clinical features and basic data of patients with vitiligo, especially those with autoimmune thyroid disease. Methods: The study was a single‐center retrospective study. A total of 1305 patients with vitiligo from June 2018 to May 2023 were included, and the clinical characteristics and basic information of the patients were recorded in detail. Results: We identified an association between sex (odds ratio [OR]: 2.380; 95% confidence interval [CI]: 1.772–1.198), vitiligo duration (OR: 1.449; 95% CI: 1.076–1.952), skin involvement exceeding 5% of the body surface area (OR: 3.764; 95% CI: 2.134–6.640), negative emotions (OR: 3.076; 95% CI: 2.292–4.127), vitiligo type (OR: 1.974; 95% CI: 1.096–3.555), family history of AITD (OR: 4.979; 95% CI: 2.687–9.225), and family history of AD (OR: 2.418; 95% CI: 1.410–4.146) and patients with vitiligo. Conclusions: For patients with statistically significant associated risk factors, differential diagnosis and early intervention should be performed. [ABSTRACT FROM AUTHOR]

Background: Large yellow croaker is highly perishable during storage because of high protein and moisture content. The degradation of the fish is mainly attributed to microbial growth and enzyme activity, so it is important to find an efficient storage method to extend its shelf life. Methodology: This study investigated the effect of a low‐voltage electrostatic field combined with partial freezing treatment on the physicochemical properties of myofibrillar protein (MP) and metabolomic analysis of large yellow croaker during preservation. The samples in chilled storage (C), partial freezing storage (PF) and 6 kV/m low‐voltage electrostatic field partial freezing storage (LVEF‐PF) were analyzed during an 18 day storage period. Results: In comparison with the C and PF groups, LVEF‐PF delayed the oxidation of MP by inhibiting the formation of carbonyl groups (2.25 nmol/mg pro), and maintaining higher sulfhydryl content (29.73 nmol/mg pro). Fourier transform infrared (FTIR) spectroscopy and fluorescence spectroscopy analysis also demonstrated that the LVEF‐PF treatment maintained the stability of the protein structure by increasing the a‐helix ratio (19.88%) and reducing the random coil ratio (17.83%). Scanning electron microscopy showed that, compared with the LVEF‐PF group, there was more degeneration and aggregation of MP in the C and PF groups after 18 days' storage. The results of untargeted metabolomic analysis showed that 415 kinds of differential metabolites were identified after storage, and the difference levels of differential metabolites were least between the samples treated with LVEF‐PF stored on the ninth day and the fresh samples. The main differential metabolic pathways during storage were amino acid metabolism and lipid metabolism. Conclusion: The LVEF‐PF treatment could maintain the stability of myofibrillar protein in large yellow croaker during storage. These results showed a potential application of the LVEF‐PF method for aquatic product preservation. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Trimethylamine N‐oxide (TMAO) is a gut‐derived atherogenic metabolite. However, the role of TMAO and its precursors in the development of stroke remains unclear. We aimed to examine the associations between metabolites in TMAO biosynthesis and stroke risk. Methods: A nested case‐control study was performed in a community‐based cohort (2013–2018, n = 16,113). We included 412 identified stroke cases and 412 controls matched by age and sex. Plasma carnitine, choline, betaine, trimethyl lysine (TML), and TMAO were measured by ultrahigh performance liquid chromatography–tandem mass spectrometry. Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) between these biomarkers and stroke risk. Results: After adjustment for body mass index, smoking, hypertension, educational attainment, and estimated glomerular filtration rate, the corresponding OR for the highest versus lowest quartile was 1.74 (95% CI: 1.16–2.61, P trend = 0.006) for total stroke and 1.81 (95% CI: 1.14–2.86, P trend = 0.020) for ischemic stroke in an essentially linear dose–response fashion. A significant association between TMAO and nonischemic stroke was shown as a J‐shape with OR for the highest versus second quartile of 5.75 (95% CI: 1.73–19.1). No meaningful significant risk association was found among plasma carnitine, choline, betaine, and TML with stroke risk. Conclusions: Increased TMAO was associated with higher stroke risk in the community‐based population, whereas the TMAO precursors carnitine, choline, betaine, and TML were not associated. Further studies are warranted to confirm these findings and to further elucidate the role of TMAO in the development of stroke. [ABSTRACT FROM AUTHOR]

Growing efforts are being invested in investigating various molecular approaches to detect minimal residual disease (MRD) and predict disease recurrence. In our study, we investigated the utility of parallel longitudinal analysis of mutation and DNA methylation profiles for predicting MRD in postoperative non‐small‐cell lung cancer (NSCLC) patients. Tumor tissues and longitudinal blood samples were obtained from 65 patients with resected stage IA‐IIIB NSCLC. Somatic mutation and DNA methylation profiling were performed using ultra‐deep targeted sequencing and targeted bisulfite sequencing, respectively. Dynamic changes in plasma‐based mutation and tumor‐informed methylation profiles, reflected as MRD score, were observed from before surgery (baseline) to postoperative follow‐up, reflecting the decrease in tumor burden of the patients with resected NSCLC. Mutations were detected from plasma samples in 63% of the patients at baseline, which significantly reduced to 23‐25% during post‐operative follow‐ups. MRD score positive rate was 95.7% at baseline, which reduced to 74% at the first and 70% at the second follow‐up. Among the 5 relapsed patients with parallel longitudinal analysis of mutation and methylation profile, elevated MRD score was observed at follow‐up between 0.5‐7 months prior to radiologic recurrence for all 5 patients. Of them, 4 patients also had concomitant increase in allelic fraction of mutations in at least 1 follow‐up time point, but one patient had no mutation detected throughout all follow‐ups. Our results demonstrate that longitudinal profiling of mutation and DNA methylation may have potential for detecting MRD and predicting recurrence in postoperative NSCLC patients.: [ABSTRACT FROM AUTHOR]

DNA methylation in transposons and other DNA repeats is conserved in plants as well as in animals. In Arabidopsis thaliana, an RNA-directed DNA methylation (RdDM) pathway directs de novo DNA methylation. We performed a forward genetic screen for suppressors of the DNA demethylase mutant ros1 and identified a novel Zinc-finger and OCRE domain-containing Protein 1 (ZOP1) that promotes Pol IV-dependent siRNA accumulation, DNA methylation, and transcriptional silencing. Whole-genome methods disclosed the genome-wide effects of zop1 on Pol IV-dependent siRNA accumulation and DNA methylation, suggesting that ZOP1 has both RdDM-dependent and -independent roles in transcriptional silencing. We demonstrated that ZOP1 is a pre-mRNA splicing factor that associates with several typical components of the splicing machinery as well as with Pol II. Immunofluorescence assay revealed that ZOP1 overlaps with Cajal body and is partially colocalized with NRPE1 and DRM2. Moreover, we found that the other development-defective splicing mutants tested including mac3a3b, mos4, mos12 and mos14 show defects in RdDM and transcriptional silencing. We propose that the splicing machinery rather than specific splicing factors is involved in promoting RdDM and transcriptional silencing. [ABSTRACT FROM AUTHOR]

One of the challenges in the development of methionine aminopeptidase (MetAP) inhibitors as antibacterial and anticancer agents is to define the metal ion actually used by MetAP in vivo and to discover MetAP inhibitors that can inhibit the metalloform that is relevant in vivo. Two distinct classes of novel nonpeptidic MetAP inhibitors that are not only potent but also highly selective for either the Mn(II) or Co(II) form have been identified. Three crystal structures of Escherichia coli MetAP complexed with the metalloform-selective inhibitors 5-(2,5-dichlorophenyl)furan-2-carboxylic acid (2), 5-[2-(trifluoromethyl)phenyl]furan-2-carboxylic acid (3) and N-cyclopentyl-N-(thiazol-2-yl)oxalamide (4) have been solved and analysis of these structures has revealed the structural basis for their metalloform-selective inhibition. The Mn(II)-form selective inhibitors (2) and (3) both use their carboxylate group to coordinate with the two Mn(II) ions at the dinuclear metal site and both adopt a non-coplanar conformation for the two aromatic rings. The unique coordination geometry of these inhibitors may determine their Mn(II)-form selectivity. In contrast, the Co(II)-form selective inhibitor (4) recruits an unexpected third metal ion, forming a trimetallic enzyme-metal-inhibitor complex. Thus, an important factor in the selectivity of (4) for the Co(II) form may be a consequence of a greater preference for a softer N,O-donor ligand for the softer Co(II).